Sequential effects of lithium on haematopoiesis.

The administration of lithium salts to haematologically normal subjects is associated with increased blood neutrophil concentrations and marrow neutrophil production and with enhanced release of colony stimulating activity (CSA) required for growth of granulocyte-macrophage progenitor cells (CFU-GM) in vitro. To examine the haematopoietic changes associated with lithium salts, mice were given LiCl daily. Blood neutrophils and serum CSA levels increased as did blood platelet concentrations. These increments were preceded by expansion of marrow neutrophil production and increased concentrations of CFU-GM as well as progenitor cells for megakaryocytes (CFU-M) and erythrocytes (BFU-E and CFU-E). An earlier and sustained increase of transplantable pluripotential stem cells (CFU-S) was detected beginning at day 2 of lithium administration. The sustained increase of CFU-S with lithium was not associated with detectable changes of endogenous stem cells (E-CFU) suggesting that a portion of the stem cell pool is resistant to the proliferative effects of lithium. These studies indicate that lithium acts initially to directly or indirectly increase marrow CFU-S with later increments of progenitor cells. The more sustained increase of blood neutrophils with lithium administration may be the result of subsequent increments of CSA resulting in enhanced marrow granulocyte production.